DOCSLIB.ORG

Orencia Safety Signal Workup Review

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Orencia Safety Signal Workup Review Department of Health and Human Services Public Health Service Food and Drug Administration Center for Drug Evaluation and Research Office of Surveillance and Epidemiology Office of Pharmacovigilance and Epidemiology Pharmacovigilance Review Date: January 8, 2020 Reviewer: Jill K Logan, PharmD, BCPS, Safety Evaluator Melissa Reyes, MD, MPH, DTMH, Medical Officer Division of Pharmacovigilance I (DPV-I) Team Leader: Michelle Hines, PharmD, BCPS, Team Leader (Acting) DPV-I Deputy Division Director: Monica Muoz, PharmD, PhD, BCPS DPV-I Product Name: Orencia (abatacept) Subjects: Angioedema Fatal hypersensitivity Application Type/Number: BLA 125118 Applicant/Sponsor: Bristol-Myers Squibb OSE RCM #: 2019-1126 TSI #: 2077 Reference ID: 4543704 TABLE OF CONTENTS Executive Summary........................................................................................................................ 1 1 Introduction............................................................................................................................. 3 1.1 Background ...................................................................................................................... 3 1.2 Pertinent Regulatory History............................................................................................ 4 1.3 Relevant Product Labeling............................................................................................... 7 2 Methods and Materials............................................................................................................ 8 2.1 Case Selection Criteria..................................................................................................... 8 2.2 Causality Assessment....................................................................................................... 9 2.3 FAERS Search Strategy ................................................................................................. 10 2.4 Literature Search ............................................................................................................ 11 3 Results................................................................................................................................... 11 3.1 FAERS and Literature Case Selection for Angioedema ................................................ 11 3.2 FAERS and Literature Case Selection for Anaphylaxis Events With Fatal Outcomes . 18 4 Discussion............................................................................................................................. 20 5 Conclusion ............................................................................................................................ 22 6 Recommendations................................................................................................................. 23 7 References............................................................................................................................. 24 8 Appendices............................................................................................................................ 26 8.1 Appendix A. Applicant-Submitted Assessment of Angioedema With Abatacept........ 26 8.2 Appendix B. FDA Adverse Event Reporting System (FAERS)................................... 30 8.3 Appendix C. FAERS Line Listing of Abatacept and Angioedema Case Series ........... 31 Reference ID: 4543704 EXECUTIVE SUMMARY This review provides the Division of Pharmacovigilance I’s (DPV-I) assessment of cases of (1) angioedema, and (2) anaphylaxis events with a fatal outcome in the FDA Adverse Event Reporting System (FAERS) database and medical literature following the identification of a pediatric case of angioedema with Orencia (abatacept). This review will inform whether the current labeling for abatacept adequately reflects the nature and severity of hypersensitivity events that have been reported in the postmarketing setting. The results of this review will be shared with the Division of Pulmonary, Allergy, and Rheumatology Products (DPARP) to assess whether regulatory action is necessary. DPV-I searched the FAERS database for reports of angioedema with abatacept through August 20, 2019, and medical literature through November 29, 2019. Our case series included 83 cases of angioedema; the majority of these were from the United States (n=61, 73.5 percent). Cases were identified with acute onset of angioedema symptoms and delayed-onset symptoms following the first abatacept exposure (n=32, 38.5 percent) or subsequent abatacept exposures (n=37, 44.6 percent). Angioedema was reported with a variety of doses and both intravenous (IV) and subcutaneous (SC) routes of administration. The symptoms reported in this case series have the potential for clinically significant or life-threatening outcomes, with respiratory symptoms defined as shortness of breath, wheezing, or difficulty breathing being reported in 24 (28.9 percent) of our cases. Furthermore, the majority of the cases within our case series reported a serious outcome (n=54, 65.1 percent), with two identified cases reporting intubation for airway protection. A positive dechallenge was reported in 27 cases (32.5 percent) and 6 cases (7.2 percent) described a positive rechallenge. The results from this analysis were limited by administration of concomitant medications with known associations with angioedema (n=16, 19.2 percent), potential for underreporting (e.g., cases with a delayed onset), database query limitations (e.g., Preferred Term coding), and limited data quality associated with postmarketing reporting. DPV-I also searched the FAERS database for reports of anaphylaxis events with fatal outcomes with abatacept through November 8, 2019, and medical literature through November 29, 2019. Our assessment of anaphylaxis events with fatal outcomes identified one case that was previously identified by the Applicant and submitted to the FDA. This case demonstrated a probable association between abatacept administration and the anaphylactic reaction with the fatal outcome. In conclusion, our assessment of postmarketing data suggests an association between abatacept and both acute- and delayed-onset angioedema. Some cases of acute-onset angioedema were associated with other symptoms of hypersensitivity (e.g., hypotension and rash) that are labeled or implied in the current warning for hypersensitivity with abatacept; however, the occurrences of delayed-onset hypersensitivity reactions and delayed-onset angioedema are not labeled. Because angioedema can be life-threatening and some cases occurred with a delayed onset (following abatacept administration) that is not usually associated with hypersensitivity events, it is important to inform prescribers of this safety issue. Furthermore, our search of the FAERS database for cases of anaphylaxis with a fatal outcome identified one case that the Applicant provided to FDA previously. Because postmarketing data cannot be used to define an incidence 1 Reference ID: 4543704 or prevalence of an event, we recommend removing case counts (i.e., “a case of…”) from the description within labeling of this event. Based on the findings of this review, DPV-recommends an update to Section 5.2 Hypersensitivity and 6.4 Postmarketing Experience to reflect the risk of angioedema with abatacept. Additionally, we recommend removal of qualifier indicating that only one case (“a case of”) of anaphylaxis with a fatal outcome has been reported because postmarketing data are limited to describe the incidence of adverse events. 2 Reference ID: 4543704 1 INTRODUCTION This review provides the Division of Pharmacovigilance I’s (DPV-I) assessment of cases of (1) angioedema, and (2) anaphylaxis events with fatal outcomes in the FDA Adverse Event Reporting System (FAERS) database and medical literature following the identification of a pediatric case of angioedema with Orencia (abatacept). This review will inform whether the current labeling for abatacept adequately reflects the nature and severity of hypersensitivity events that have been reported in the postmarketing setting. The results of this review will be shared with the Division of Pulmonary, Allergy, and Rheumatology Products (DPARP) to assess whether regulatory action is necessary. 1.1 BACKGROUND Abatacept is a fusion protein that inhibits T cell activation.1 It is available for intravenous (IV) and subcutaneous (SC) administration. Abatacept is indicated for the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and psoriatic arthritis (PsA). 1.1.1 Angioedema Angioedema is defined as deep dermal, subcutaneous, and/or mucosal membrane (including the respiratory and gastrointestinal tracts) swelling that is abrupt in onset.2-4 Although angioedema can occur in any part of the body, it most frequently involves the face (e.g., eyes, lips, mouth, tongue), extremities, or genitalia.5 Angioedema is typically self-limiting with most lesions resolving within 72 hours and the involved tissue returning to baseline without sequalae.4 Complications of angioedema, however, can be fatal as edema involving the respiratory tracta can lead to impaired oxygenation and asphyxiation.4,5 Angioedema has multiple etiologies and may actually describe a group of disorders with a common clinical expression.2 Types of angioedema are numerous and include hereditary and acquired angioedema, idiopathic angioedema, chronic urticaria-associated angioedema, vasculitis-induced angioedema, drug- induced angioedema, and others.4 Current labeling for
Load more

Recommended publications
  • Arthritis and Coeliac Disease
    Ann Rheum Dis: first published as 10.1136/ard.44.9.592 on 1 September 1985. Downloaded from Annals of the Rheumatic Diseases 1985, 44, 592-598 Arthritis and coeliac disease J T BOURNE,' P KUMAR,2 E C HUSKISSON,' R MAGEED 3 D J UNSWORTH,3 AND J A WOJTULEWSKI4 From the Departments of 'Rheumatology and 2Gastroenterology, St Bartholomew's Hospital, West Smithfield, London ECIA 7BE; the 3Bone and Joint Research Unit, London Hospital Medical College, London El; and 4St Mary's Hospital, Eastbourne SUMMARY We report six patients with coeliac disease in whom arthritis was prominent at diagnosis and who improved with dietary therapy. Joint pain preceded diagnosis by up to three years in five patients and 15 years in one patient. Joints most commonly involved were lumbar spine, hips, and knees (four cases). In three cases there were no bowel symptoms. All were seronegative. X-rays were abnormal in two cases. HLA-type Al, B8, DR3 was present in five and B27 in two patients. Circulating immune complexes showed no consistent pattern before or after treatment. Coeliac disease was diagnosed in all patients by jejunal biopsy, and joint symptoms in all responded to a gluten-free diet. Gluten challenge (for up to three weeks) failed to provoke arthritis in three patients tested. In a separate study of 160 treated coeliac patients attending regular follow up no arthritis attributable to coeliac disease and no ankylosing was in a group spondylitis identified, though control of 100 patients with Crohn's disease thecopyright. expected incidence of seronegative polyarthritis (23%) and ankylosing spondylitis (5%) was found (p<0.01).
    [Show full text]
  • Infection of the CNS by Scedosporium Apiospermum After Near Drowning
    205 CASE REPORT J Clin Pathol: first published as 10.1136/jcp.2003.8680 on 27 January 2004. Downloaded from Infection of the CNS by Scedosporium apiospermum after near drowning. Report of a fatal case and analysis of its confounding factors P A Kowacs, C E Soares Silvado, S Monteiro de Almeida, M Ramos, K Abra˜o, L E Madaloso, R L Pinheiro, L C Werneck ............................................................................................................................... J Clin Pathol 2004;57:205–207. doi: 10.1136/jcp.2003.8680 from the usual 15 days to up to 130 days. This type of This report describes a fatal case of central nervous system infection causes granulomata or abscesses and neutrophilic pseudallescheriasis. A 32 year old white man presented with meningitis.125 headache and meningismus 15 days after nearly drowning in a swine sewage reservoir. Computerised tomography and ‘‘In cases secondary to aspiration after near drowning, magnetic resonance imaging of the head revealed multiple once in the bloodstream, fungi seed into several sites but brain granulomata, which vanished when steroid and broad develop mainly in the central nervous system’’ spectrum antimicrobial and antifungal agents, in addition to dexamethasone, were started. Cerebrospinal fluid analysis To date, few cases of CNS pseudallescheriasis have been 2 disclosed a neutrophilic meningitis. Treatment with antibiotics described. However, such a diagnosis must should always be sought in individuals who have suffered near drowning in and amphotericin B, together with fluconazole and later standing polluted streams, ponds of water or sewage, or pits itraconazole, was ineffective. Miconazole was added with manure. through an Ommaya reservoir, but was insufficient to halt The case of a man who acquired a CNS P boydii infection the infection.
    [Show full text]
  • Conditions Related to Inflammatory Arthritis
    Conditions Related to Inflammatory Arthritis There are many conditions related to inflammatory arthritis. Some exhibit symptoms similar to those of inflammatory arthritis, some are autoimmune disorders that result from inflammatory arthritis, and some occur in conjunction with inflammatory arthritis. Related conditions are listed for information purposes only. • Adhesive capsulitis – also known as “frozen shoulder,” the connective tissue surrounding the joint becomes stiff and inflamed causing extreme pain and greatly restricting movement. • Adult onset Still’s disease – a form of arthritis characterized by high spiking fevers and a salmon- colored rash. Still’s disease is more common in children. • Caplan’s syndrome – an inflammation and scarring of the lungs in people with rheumatoid arthritis who have exposure to coal dust, as in a mine. • Celiac disease – an autoimmune disorder of the small intestine that causes malabsorption of nutrients and can eventually cause osteopenia or osteoporosis. • Dermatomyositis – a connective tissue disease characterized by inflammation of the muscles and the skin. The condition is believed to be caused either by viral infection or an autoimmune reaction. • Diabetic finger sclerosis – a complication of diabetes, causing a hardening of the skin and connective tissue in the fingers, thus causing stiffness. • Duchenne muscular dystrophy – one of the most prevalent types of muscular dystrophy, characterized by rapid muscle degeneration. • Dupuytren’s contracture – an abnormal thickening of tissues in the palm and fingers that can cause the fingers to curl. • Eosinophilic fasciitis (Shulman’s syndrome) – a condition in which the muscle tissue underneath the skin becomes swollen and thick. People with eosinophilic fasciitis have a buildup of eosinophils—a type of white blood cell—in the affected tissue.
    [Show full text]
  • Adverse Events After Immunisation- Common and Uncommon
    Adverse events following Immunisation Common and Uncommon Dr Anna Clarke National Immunisation Office September 2016 www.immunisation.ie Abbreviations • ADR-adverse drug reaction • AE- adverse event • AEFI-adverse event following immunisation • SAE- serious adverse event • SUSAR-suspected unexpected serious adverse reaction Definitions • Adverse Drug Reaction – A response to a drug which is noxious and unintended, …occurs at doses normally used for the prophylaxis,.. or therapy of disease, … • Adverse Event – Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment Definitions Adverse Event Following Immunization (AEFI) Any untoward medical occurrence which follows immunisation and which does not necessarily have a causal relationship with the usage of the vaccine. The adverse event may be any unfavourable or unintended sign, abnormal laboratory finding, symptom or disease. AEFI 1. Loose definition to encourage reporting - does not restrict type of event - does not limit the time after immunisation - events, not reactions, are reported 2. Belief that immunisation was responsible may be correct, incorrect, or impossible to assess 3. Does not imply causality AEFIs Mild Reactions – Common – Include pain, swelling, fever, irritability, malaise – Self-limiting, seldom requiring symptomatic treatment But - important to inform parents about such events so they know about them Serious Adverse Event • Fatal • Life-threatening •
    [Show full text]
  • Hypersensitivity Reactions (Types I, II, III, IV)
    Hypersensitivity Reactions (Types I, II, III, IV) April 15, 2009 Inflammatory response - local, eliminates antigen without extensively damaging the host’s tissue. Hypersensitivity - immune & inflammatory responses that are harmful to the host (von Pirquet, 1906) - Type I Produce effector molecules Capable of ingesting foreign Particles Association with parasite infection Modified from Abbas, Lichtman & Pillai, Table 19-1 Type I hypersensitivity response IgE VH V L Cε1 CL Binds to mast cell Normal serum level = 0.0003 mg/ml Binds Fc region of IgE Link Intracellular signal trans. Initiation of degranulation Larche et al. Nat. Rev. Immunol 6:761-771, 2006 Abbas, Lichtman & Pillai,19-8 Factors in the development of allergic diseases • Geographical distribution • Environmental factors - climate, air pollution, socioeconomic status • Genetic risk factors • “Hygiene hypothesis” – Older siblings, day care – Exposure to certain foods, farm animals – Exposure to antibiotics during infancy • Cytokine milieu Adapted from Bach, JF. N Engl J Med 347:911, 2002. Upham & Holt. Curr Opin Allergy Clin Immunol 5:167, 2005 Also: Papadopoulos and Kalobatsou. Curr Op Allergy Clin Immunol 7:91-95, 2007 IgE-mediated diseases in humans • Systemic (anaphylactic shock) •Asthma – Classification by immunopathological phenotype can be used to determine management strategies • Hay fever (allergic rhinitis) • Allergic conjunctivitis • Skin reactions • Food allergies Diseases in Humans (I) • Systemic anaphylaxis - potentially fatal - due to food ingestion (eggs, shellfish,
    [Show full text]
  • Reactive Arthritis Information Booklet
    Reactive arthritis Reactive arthritis information booklet Contents What is reactive arthritis? 4 Causes 5 Symptoms 6 Diagnosis 9 Treatment 10 Daily living 16 Diet 18 Complementary treatments 18 How will reactive arthritis affect my future? 19 Research and new developments 20 Glossary 20 We’re the 10 million people living with arthritis. We’re the carers, researchers, health professionals, friends and parents all united in Useful addresses 25 our ambition to ensure that one day, no one will have to live with Where can I find out more? 26 the pain, fatigue and isolation that arthritis causes. Talk to us 27 We understand that every day is different. We know that what works for one person may not help someone else. Our information is a collaboration of experiences, research and facts. We aim to give you everything you need to know about your condition, the treatments available and the many options you can try, so you can make the best and most informed choices for your lifestyle. We’re always happy to hear from you whether it’s with feedback on our information, to share your story, or just to find out more about the work of Versus Arthritis. Contact us at [email protected] Registered office: Versus Arthritis, Copeman House, St Mary’s Gate, Chesterfield S41 7TD Words shown in bold are explained in the glossary on p.20. Registered Charity England and Wales No. 207711, Scotland No. SC041156. Page 2 of 28 Page 3 of 28 Reactive arthritis information booklet What is reactive arthritis? However, some people find it lasts longer and can have random flare-ups years after they first get it.
    [Show full text]
  • Reviewer Guidance
    Reviewer Guidance Conducting a Clinical Safety Review of a New Product Application and Preparing a Report on the Review U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) February 2005 Good Review Practices Reviewer Guidance Conducting a Clinical Safety Review of a New Product Application and Preparing a Report on the Review Additional copies are available from: Office of Training and Communication Division of Drug Information, HFD-240 Center for Drug Evaluation and Research Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 (Tel) 301-827-4573 http://www.fda.gov/cder/guidance/index.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) February 2005 Good Review Practices TABLE OF CONTENTS I. INTRODUCTION............................................................................................................. 1 II. GENERAL GUIDANCE ON THE CLINICAL SAFETY REVIEW .......................... 2 A. Introduction....................................................................................................................................2 B. Explanation of Terms ....................................................................................................................3 C. Overview of the Safety Review .....................................................................................................4 D. Differences in Approach to Safety and Effectiveness Data ........................................................4
    [Show full text]
  • Joint Pain and Sjögren’S Syndrome
    Joint Pain and Sjögren’s Syndrome Alan N. Baer, MD, FACP Alan N. Baer, MD, FACP Associate Professor of Medicine Division of Rheumatology Johns Hopkins University School of Medicine Director, Jerome Greene Sjogren's Syndrome Clinic 5200 Eastern Avenue Mason F. Lord Bldg. Center Tower Suite 4100, Room 413 Baltimore MD 21224 Phone (410) 550-1887 Fax (410) 550-6255 In 1930, Henrik Sjögren, a Swedish ophthalmologist, examined a woman with rheumatoid arthritis who had extreme dryness of her eyes and mouth and filamentary keratitis, an eye condition related to her lack of tears (1). He became fascinated by this unusual debilitating condition and subsequently evaluated 18 additional women with the same combination of findings. He described this new syndrome as “keratoconjunctivitis sicca” in his postdoctoral thesis. Thirteen of the 19 women had chronic inflammatory arthritis. We would now classify these 13 women as having secondary Sjögren’s syndrome (SS), occurring in the context of rheumatoid arthritis. However, joint pain constitutes one of the most common symptoms of the primary form of SS, defined as SS occurring in the absence of an underlying rheumatic disease. In a recent survey of SS patients belonging to the French Sjögren’s Syndrome Society (Association Française du Gougerot-Sjögren et des Syndromes Secs), 81% reported significant joint and muscle pain (2). In this article, the joint manifestations of primary SS will be reviewed. A few definitions are needed for the reader. Although the term “arthritis” was originally applied to conditions causing joint inflammation, it now includes disorders in which the joint has become damaged by degenerative, metabolic, or traumatic processes.
    [Show full text]
  • AHRQ Quality Indicators Fact Sheet
    AHRQ Quality Indicators Toolkit Fact Sheet on Inpatient Quality Indicators What are the Inpatient Quality Indicators? The Inpatient Quality Indicators (IQIs) include 28 provider-level indicators established by the Agency for Healthcare Research and Quality (AHRQ) that can be used with hospital inpatient discharge data to provide a perspective on quality. They are grouped into the following four sets: • Volume indicators are proxy, or indirect, measures of quality based on counts of admissions during which certain intensive, high-technology, or highly complex procedures were performed. They are based on evidence suggesting that hospitals performing more of these procedures may have better outcomes. • Mortality indicators for inpatient procedures include procedures for which mortality has been shown to vary across institutions and for which there is evidence that high mortality may be associated with poorer quality of care. • Mortality indicators for inpatient conditions include conditions for which mortality has been shown to vary substantially across institutions and for which evidence suggests that high mortality may be associated with deficiencies in the quality of care. • Utilization indicators examine procedures whose use varies significantly across hospitals and for which questions have been raised about overuse, underuse, or misuse. Mortality for Selected Procedures and Mortality for Selected Conditions are composite measures that AHRQ established in 2008. Each composite is estimated as a weighted average, across a set of IQIs, of the ratio of a hospital’s observed rate (OR) to its expected rate (ER), based on a reference population: OR/ER. The IQI-specific ratios are adjusted for reliability before they are averaged, to minimize the influence of ratios that are high or low at a specific hospital by chance.
    [Show full text]
  • Interventions for Treating Acute High Altitude Illness
    This document is downloaded from DR‑NTU (https://dr.ntu.edu.sg) Nanyang Technological University, Singapore. Interventions for treating acute high altitude illness Simancas‑Racines, Daniel; Arevalo‑Rodriguez, Ingrid; Osorio, Dimelza; Franco, Juan V.A.; Xu, Yihan; Hidalgo, Ricardo 2018 Simancas‑Racines, D., Arevalo‑Rodriguez, I., Osorio, D., Franco, J. V., Xu, Y., & Hidalgo, R. Interventions for treating acute high altitude illness. Cochrane Database of Systematic Reviews. (6), CD009567‑. doi:10.1002/14651858.CD009567.pub2 https://hdl.handle.net/10356/82999 https://doi.org/10.1002/14651858.CD009567.pub2 © 2018 The Cochrane Collaboration. All rights reserved. This paper was published by John Wiley & Sons, Ltd. in Cochrane Database of Systematic Reviews and is made available with permission of The Cochrane Collaboration. Downloaded on 28 Sep 2021 20:37:23 SGT [Intervention Review] Interventions for treating acute high altitude illness Daniel Simancas-Racines1, Ingrid Arevalo-Rodriguez1,2,3, Dimelza Osorio1, Juan VA Franco4, Yihan Xu5, Ricardo Hidalgo1 1Cochrane Ecuador. Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador. 2Clinical Biostatistics Unit, Hospital Ramon y Cajal (IRYCIS), Madrid, Spain. 3CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 4Argentine Cochrane Centre, Instituto Universi- tario Hospital Italiano, Buenos Aires, Argentina. 5Wee Kim Wee School of Communication and Information, Nanyang Technological University, Singapore City, Singapore Contact address: Daniel Simancas-Racines, Cochrane Ecuador. Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador. [email protected], [email protected].
    [Show full text]
  • A Dash of Dermatology and a Pinch of Rheumatology
    A dash of dermatology and a pinch of rheumatology Sarita Nori, MD, FAAD Dermatology Atrius Health I have no conflicts of interest to disclose. 2 . Points in white = fun factoids . Points in blue = important for clinical practice; practice gaps. (Basically what you want to remember from this talk.) OUTLINE . Some clinical pearls . Treatment . Diagnosis . Update in Dermatology: . Biologics for Psoriasis - because many of your patients are on these meds now. Biologic for Atopic dermatitis – finally something new! Treatment pearls . For all itch/dermatitis: maximize anti histamines. - Zyrtec/Claritin/Allegra bid, - plus Benadryl or Hydroxyzine qhs, with intent of sedation Poison ivy - Can avoid oral steroids. Use higher topical steroids TID, + maximal anti histamines. - Poison ivy adjunct care: important to dissolve the oil from all objects that may have been exposed. Eg pets, pet collars & leashes, gardening gloves, hats, socks, shoes, watch straps, earrings etc. This is often why the rash seems to get worse despite treatment, or spreads a lot, or recurs even though it was getting better Treatment pearls . Tinea versicolor: > treat with Diflucan 400mg po x 2 doses, 1 week apart. Pityriasis Rosea: > Acyclovir 800mg 5 times /day x 1 week => 79% pts cleared by day 14. Das et al. Indian Dermatol Online J. 2015 May-Jun; 6(3): 181–184. • Seb derm on scalp/psoriasis on scalp/dandruff/itchy scalp: Ketoconazole shampoo daily, clobetasol solution qd for 2-4 weeks • Testing in allergy dept is not = skin allergy testing (patch testing). Skin contact allergies develop after multiple exposures, so not usually a new exposure. 6 MORE TREATMENT PEARLS .
    [Show full text]
  • Guideline on Clinical Investigation of Medicinal Products for the Treatment of Rheumatoid Arthritis
    14 December 2017 CPMP/EWP/556/95 Rev. 2 Committee for Medicinal Products for Human Use (CHMP) Guideline on clinical investigation of medicinal products for the treatment of rheumatoid arthritis Draft Agreed by Rheumatology-Immunology Working Party (RIWP) December 2011 Adoption by CHMP for release for consultation 5 December 2011 End of consultation (deadline for comments) 05 June 2012 Agreed by Rheumatology-Immunology Working Party (RIWP) March 2015 Adoption by CHMP 20 March 2015 Start of public consultation 4 June 2015 End of consultation (deadline for comments) 29 November 2015 Agreed by Rheumatology-Immunology Working Party (RIWP) 24 November 2017 Adoption by CHMP 14 December 2017 Date of coming into effect 01 July 2018 This guideline replaces the “Points to consider on the clinical investigation of medicinal products other than NSAIDS in rheumatoid arthritis (CPMP/EWP/556/95 REV. 1)” Keywords Rheumatoid arthritis, Disease Modifying Anti-Rheumatic Drugs, clinical development, CHMP, EMA, guideline 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Guideline on clinical investigation of medicinal products for the treatment of rheumatoid arthritis Table of contents List of abbreviations .................................................................................... 3 Executive
    [Show full text]